Lymphocyte respiration in children with Trisomy 21

<p>Abstract</p> <p>Background</p> <p>This study measured lymphocyte mitochondrial O₂ consumption (cellular respiration) in children with trisomy 21.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells were isolated from whole blood of trisomy 21 and control children and these cells were immediately used to measure cellular respiration rate. [O₂] was determined as a function of time from the phosphorescence decay rates (1/τ) of Pd (II)-<it>meso</it>-tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin. In sealed vials containing lymphocytes and glucose as a respiratory substrate, [O₂] declined linearly with time, confirming the zero-order kinetics of O₂ conversion to H₂O by cytochrome oxidase. The rate of respiration (<it>k</it>, in μM O₂ min^-1), thus, was the negative of the slope of [O₂] <it>vs.</it> time. Cyanide inhibited O₂ consumption, confirming that oxidation occurred in the mitochondrial respiratory chain.</p> <p>Results</p> <p>For control children (age = 8.8 ± 5.6 years, n = 26), the mean (± SD) value of <it>k</it>_<it>c</it> (in μM O₂ per min per 10⁷ cells) was 1.36 ± 0.79 (coefficient of variation, Cv = 58%; median = 1.17; range = 0.60 to 3.12; -2SD = 0.61). For children with trisomy 21 (age = 7.2 ± 4.6 years, n = 26), the values of <it>k</it>_<it>c</it> were 0.82 ± 0.62 (Cv = 76%; median = 0.60; range = 0.20 to 2.80), <it>p</it><0.001. Similar results (<it>p</it><0.000) were obtained after excluding the five trisomy 21 children with elevated serum TSH (values >6.1 mU/L). Fourteen of 26 (54%) children with trisomy 21 had <it>k</it>_<it>c</it> values of 0.20 to 0.60 (i.e., <−2SD). The values of <it>k</it>_<it>c</it> positively correlated with body-mass index (BMI, <it>R</it> >0.302), serum creatinine (<it>R</it> >0.507), blood urea nitrogen (BUN, <it>R</it> >0.535) and albumin (<it>R</it> >0.446).</p> <p>Conclusions</p> <p>Children with trisomy 21 in this study have reduced lymphocyte bioenergetics. The clinical importance of this finding requires further studies.</p